Kamimura Kenya, Liu Dexi
Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, 527 Salk Hall, Pittsburgh, PA 15261, USA.
AAPS J. 2008 Dec;10(4):589-95. doi: 10.1208/s12248-008-9067-y. Epub 2008 Dec 13.
The liver is a key organ for numerous metabolic pathways and involves many inherited diseases that, although being different in their pathology, are often caused by lack or overproduction of a critical gene product in the diseased cells. In principle, a straightforward method to fix such problem is to introduce into these cells with a gene-coding sequence to provide the missing gene product or with the nucleic acid sequence to inhibit production of the excessive gene product. Practically, however, success of nucleic acid-based pharmaceutics is dependent on the availability of a method capable of delivering nucleic acid sequence in the form of DNA or RNA to liver cells. In this review, we will summarize the progress toward the development of physical methods for nucleic acid delivery to the liver. Emphasis is placed on the mechanism of action, pros, and cons of each method developed so far. We hope the information provided will encourage new endeavor to improve the current methodologies or develop new strategies that will lead to safe and effective delivery of nucleic acids to the liver.
肝脏是众多代谢途径的关键器官，涉及许多遗传性疾病。这些疾病虽然病理不同，但往往是由患病细胞中关键基因产物的缺乏或过量产生所致。原则上，解决此类问题的直接方法是将编码基因的序列导入这些细胞，以提供缺失的基因产物，或者导入核酸序列以抑制过量基因产物的产生。然而，实际上，基于核酸的药物的成功取决于能否有一种方法能够将DNA或RNA形式的核酸序列递送至肝细胞。在本综述中，我们将总结向肝脏递送核酸的物理方法的发展进展。重点在于目前已开发的每种方法的作用机制、优缺点。我们希望所提供的信息能够鼓励人们做出新的努力，以改进现有方法或开发新策略，从而实现向肝脏安全有效地递送核酸。
